Evoked EEG Responses to TMS Targeting Regions Outside the Primary Motor Cortex and Their Test-Retest Reliability.

Transcranial magnetic stimulation (TMS)-evoked electroencephalography (EEG) potentials (TEPs) provide unique insights into cortical excitability and connectivity. However, confounding EEG signals from auditory and somatosensory co-stimulation complicate TEP interpretation. Our optimized sham procedure established with TMS of primary motor cortex (Gordon in JAMA 245:118708, 2021) differentiates direct cortical EEG responses to TMS from those caused by peripheral sensory inputs. Using this approach, this study aimed to investigate TEPs and their test-retest reliability when targeting regions outside the primary motor cortex, specifically the left angular gyrus, supplementary motor area, and medial prefrontal cortex. We conducted three identical TMS-EEG sessions one week apart involving 24 healthy participants. In each session, we targeted the three areas separately using a figure-of-eight TMS coil for active TMS, while a second coil away from the head produced auditory input for sham TMS. Masking noise and electric scalp stimulation were applied in both conditions to achieve matched EEG responses to peripheral sensory inputs. High test-retest reliability was observed in both conditions. However, reliability declined for the 'cleaned' TEPs, resulting from the subtraction of evoked EEG response to the sham TMS from those to the active, particularly for latencies > 100 ms following the TMS pulse. Significant EEG differences were found between active and sham TMS at latencies < 90 ms for all targeted areas, exhibiting distinct spatiotemporal characteristics specific to each target. In conclusion, our optimized sham procedure effectively reveals EEG responses to direct cortical activation by TMS in brain areas outside primary motor cortex. Moreover, we demonstrate the impact of peripheral sensory inputs on test-retest reliability of TMS-EEG responses.

The impact of vitamin D changes during pregnancy on the development of maternal adverse events: a random forest analysis.

BACKGROUND: Maternal vitamin D deficiency during pregnancy has been associated with various maternal adverse events (MAE). However, the evidence regarding the effect of vitamin D supplementation on these outcomes is still inconclusive. METHODS: This secondary analysis utilized a case-control design. 403 samples with MAE and 403 samples without any outcomes were selected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy study. Random forest (RF) analysis was used to evaluate the effect of maternal vitamin D changes during pregnancy on MAE. RESULTS: The results showed that women who remained deficient (35.2%) or who worsened from sufficient to deficient (30.0%) had more MAE than women who improved (16.4%) or stayed sufficient (11.8%). The RF model had an AUC of 0.74, sensitivity of 72.6%, and specificity of 69%, which indicate a moderate to high performance for predicting MAE. The ranked variables revealed that systolic blood pressure is the most important variable for MAE, followed by diastolic blood pressure and vitamin D changes during pregnancy. CONCLUSION: This study provides evidence that maternal vitamin D changes during pregnancy have a significant impact on MAE. Our findings suggest that monitoring and treatment of vitamin D deficiency during pregnancy may be a potential preventive strategy for reducing the risk of MAE. The presented RF model had a moderate to high performance for predicting MAE.

Untangling TMS-EEG responses caused by TMS versus sensory input using optimized sham control and GABAergic challenge.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) elegantly probes the excitability and connectivity of the human brain. However, TMS-EEG signals inevitably also contain sensory-evoked responses caused by TMS-associated auditory and somatosensory inputs, constituting a substantial confounding factor. Here we applied our recently established optimized SHAM protocol (Gordon et al., Neuroimage 2021:118708) to disentangle TMS-EEG responses caused by TMS vs. sensory input. One unresolved question is whether these responses superimpose without relevant interaction, a requirement for their disaggregation by the optimized SHAM approach. We applied in 20 healthy subjects a pharmacological intervention using a single oral dose of 20 mg of diazepam, a positive modulator of GABAA receptors. Diazepam decreased the amplitudes of the P60 and P150 components specifically in the ACTIVE TMS and/or the ACTIVE TMS minus SHAM conditions but not in the SHAM condition, pointing to a response caused by TMS. In contrast, diazepam suppressed the amplitude of the N100 component indiscriminately in the ACTIVE TMS and SHAM conditions but not in the ACTIVE TMS minus SHAM condition, pointing to a response caused by sensory input. Moreover, diazepam suppressed the beta-band response observed in the motor cortex specifically after ACTIVE TMS and ACTIVE TMS minus SHAM. These findings demonstrate a lack of interaction of TMS-EEG responses caused by TMS vs. sensory input and validate optimized SHAM-controlled TMS-EEG as an appropriate approach to untangle these TMS-EEG responses. This knowledge will enable the proficient use of TMS-EEG to probe the physiology of the human cortex. KEY POINTS: Optimized SHAM disentangles TMS-EEG responses caused by TMS vs. sensory input. Diazepam differentially modulates TMS-EEG responses caused by TMS vs. sensory input. Diazepam modulation of P60 and P150 indicate TMS-EEG responses caused by TMS. Diazepam modulation of N100 indicate a TMS-EEG response caused by sensory input.

Future climate-driven drought events across Lake Urmia, Iran.

Climate change has increased the vulnerability of arid and semi-arid regions to recurrent and prolonged meteorological droughts. In light of this, our study has sought to assess the nature of future meteorological drought in Lake Urmia basin, Iran, within the context of future climate projections. To achieve this, data from 54 general circulation models (GCMs) was calibrated against both in situ and Global Precipitation Climatology Centre datasets. These GCMs were then employed to project drought conditions expected over 2016-2046 under RCP2.6 and RCP8.5 as the most optimistic and pessimistic scenarios, respectively. To provide a comprehensive analysis, these RCPs were combined with two different time scale Standardized Precipitation Index (SPI), leading to eight different scenarios. The SPI was calculated over two temporal scales for the past (1985-2015) and future (2016-2046), including the medium-term (SPI-6) and long-term (SPI-18) index. Results showed that while precipitation is expected to increase by up to 34%, parts of the basin are projected to face severe and prolonged droughts under both RCPs. The most severe drought event is expected to occur around 2045-2046 under the most pessimistic RCP8.5 scenario. Severe droughts with low frequency are also anticipated to increase under other scenarios. By characterizing meteorological drought conditions for Lake Urmia basin under future climate conditions, our findings call for urgent action for adaptation strategies to mitigate the future adverse effects of drought in this region and other regions facing similar challenges. Overall, this study provides valuable insight into the impacts of climate change on future droughts that can adversely influence water resources in arid and semi-arid regions.

Relationship between vitamin D status in the first trimester of the pregnancy and gestational weight gain: a mediation analysis.

PURPOSE: To evaluate the total, and direct effects of vitamin D, measured by circulating 25-hydroxyvitamin D [25(OH)D] levels, on GWG after adjustment for confounding variables, and then assess the indirect effects by demonstrating the role of gestational age at birth as a mediator in this association. METHODS: Data collected in "Khuzestan Vitamin D Deficiency Screening Program in Pregnancy" were used for the present study; it included the data of 900 pregnant women referred to the health centers of Shushtar (Khuzestan Province, Iran), whose vitamin D status during the third trimester of pregnancy was available. A mediation analysis was applied to detect the causal relationship between serum level of 25(OH)D, covariates (maternal age, parity, education level, and baseline maternal weight), mediator (gestational age), and outcome (GWG). RESULTS: Of 900 pregnant women referred to the health centers, a total of 726 eligible participants were analyzed for the study. The adjusted total effect of vitamin D on GWG was estimated 0.07 (95% CI 0.06, 0.09; P = 0.000). This study also revealed adjusted direct effect of vitamin D on GWG was statistically significant 0.02 (95% CI: 0.003, 0.04; P = 0.021). In addition, the adjusted indirect effect of this micronutrient on GWG by considering gestational age as a mediator was found to be significant [0.05 (95% CI 0.04, 0.06; P = 0.000)]. This study revealed an increase in the trend of weight gain during pregnancy trimesters for women with different levels of 25(OH)D; however, women with severe vitamin D deficiency had the lowest speed as compared to moderate and normal levels. CONCLUSION: This study shows that maternal vitamin D status directly affects the gestational weight gain independent of gestational age. Therefore, the detection and treatment of women with vitamin D inadequacy can directly improve the trend of their weight gain in addition to its indirect effect on reducing the risk of preterm delivery.

Involvement of muscarinic acetylcholine receptor-mediated cholinergic neurotransmission in TMS-EEG responses.

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS-EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS-EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS-EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS-EEG physiology, providing insights for its application in physiological and clinical research.

The association between oral contraceptive pills and ovarian cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Previous study results have been inconclusive, so this meta-analysis aims to evaluate the association between ovarian cancer and oral contraceptive pills (OCPs). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched to identify studies on the association between OCPs and ovarian cancer from January 1, 2000 through February 5, 2023. The pooled relative risk (RR) and odds ratio (OR) were used to measure this relationship. RESULTS: A total of 67 studies were included. In the association between ever-use compared with never-use of OCPs and ovarian cancer risk, the pooled RR in cohort studies was 0.69 [95% CI: 0.61, 0.78]. For the relationship between duration of OCPs use and ovarian cancer in the cohort studies, no association between duration of use1-12 months 0.92 [95% CI: 0.82, 1.03] and duration of use 13-60 months 0.87 [95% CI: 0.73, 1.04], but there is a statistically significant inverse relationship between duration of use 61-120 months 0.62 [95% CI: 0.48, 0.81] and more than 120 months 0.51 [95% CI: 0.32, 0.80] and ovarian cancer. For the relationship between OCPs and histological subtype of epithelial ovarian cancer in the cohort studies, the pooled RR for invasive was 0.70 [95% CI: 0.56, 0.87], but no association between OCPs and borderline ovarian cancer 0.64 [95% CI: 0.31, 1.31]. CONCLUSION: Our analysis shows a statistically significant inverse relationship between ever-use compared to never-use of OCPs and ovarian cancer risk,and also between invasive cancer and OCPs. By increasing the duration of OCPs use, the risk of ovarian cancer decreased.

Maternal weight latent trajectories and associations with adverse pregnancy outcomes using a smoothing mixture model.

Class membership is a critical issue in health data sciences. Different types of statistical models have been widely applied to identify participants within a population with heterogeneous longitudinal trajectories. This study aims to identify latent longitudinal trajectories of maternal weight associated with adverse pregnancy outcomes using smoothing mixture model (SMM). Data were collected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy. We applied the data of 877 pregnant women living in Shooshtar city, whose weights during the nine months of pregnancy were available. In the first step, maternal weight was classified and participants were assigned to only one group for which the estimated trajectory is the most similar to the observed one using SMM; then, we examined the associations of identified trajectories with risk of adverse pregnancy endpoints by applying logistic regression. Three latent trajectories for maternal weight during pregnancy were identified and named as low, medium and high weight trajectories. Crude estimated odds ratio (OR) for icterus, preterm delivery, NICU admission and composite neonatal events shows significantly higher risks in trajectory 1 (low weight) compared to trajectory 2 (medium weight) by 69% (OR = 1.69, 95%CI 1.20, 2.39), 82% (OR = 1.82, 95%CI 1.14, 2.87), 77% (OR = 1.77, 95%CI 1.17, 2.43), and 85% (OR = 1.85, 95%CI 1.38, 2.76), respectively. Latent class trajectories of maternal weights can be accurately estimated using SMM. It is a powerful means for researchers to appropriately assign individuals to their class. The U-shaped curve of association between maternal weight gain and risk of maternal complications reveals that the optimum place for pregnant women could be in the middle of the growth curve to minimize the risks. Low maternal weight trajectory compared to high had even a significantly higher hazard for some neonatal adverse events. Therefore, appropriate weight gain is critical for pregnant women.Trial registration International Standard Randomized Controlled Trial Number (ISRCTN): 2014102519660N1; http://www.irct.ir/searchresult.php?keyword=&id=19660&number=1&prt=7805&total=10&m=1 (Archived by WebCite at http://www.webcitation.org/6p3lkqFdV ).

Mode of delivery and maternal vitamin D deficiency: an optimized intelligent Bayesian network algorithm analysis of a stratified randomized controlled field trial.

This study aimed to elucidate the algorithm of various influential factors relating to the association between 25-hydroxyvitamin D (25(OH)D) concentration at delivery and mode of delivery. The investigation constituted a secondary analysis using data collected as part of the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy, which is a stratified randomized vitamin D supplementation-controlled trial comprising 1649 eligible pregnant women. The Bayesian Network (BN) method was utilized to determine the association algorithm between diverse influential factors associated with maternal vitamin D and mode of delivery. The optimized intelligent BN algorithm revealed that women presenting with moderate (35.67%; 95% CI: 33.36-37.96) and severe vitamin D deficiency (47.22%; 95% CI: 44.81-49.63) at delivery were more likely to undergo cesarean section than those presenting with normal concentrations of this nutritional hormone (18.62%; 95% CI: 16.74-20.5). The occurrence probabilities of preeclampsia in mothers with normal, moderate, and severe vitamin D deficiency at delivery were (1.5%; 95% CI: 0.92-2.09), (14.01%; 95% CI: 12.33-15.68), and (26.81%; 95% CI: 24.67-28.95), respectively. Additionally, mothers with moderate (11.81%; 95% CI: 10.25-13.36) and severe (27.86%; 95% CI: 25.69-30.02) vitamin D deficiency exhibited a higher probability of preterm delivery in comparison to those presenting with normal concentrations (1.12%; 95% CI: 0.62-1.63). This study demonstrated that the vitamin D status of pregnant women at delivery could directly affect the mode of delivery and indirectly through maternal complications, such as preeclampsia and preterm delivery, leading to a higher occurrence probability of cesarean section.

Vigilance described by the time-on-task effect in EEG activity during a cued Go/NoGo task.

Vigilance refers to the ability to maintain attention and to remain alert to stimuli in prolonged and monotonous tasks. Vigilance decrement describes the decline in performance in the course of such sustained attention tasks. Time-related alterations in attention have been found to be associated with changes in EEG. We investigated these time-on-task effects on the basis of changes in the conventional EEG spectral bands with the aim of finding a compound measure of vigilance. 148 healthy adults performed a cued Go/NoGo task that lasted approximately 21 min. Behavioural performance was examined by comparing the number of errors in the first and last quarters of the task using paired t-test. EEG data were epoched per trial, and time-on-task effects were modelled by using multiple linear regression, with frequency spectra band power values as independent variables and trial number as the dependent variable. Behavioural performance decreased in terms of omission errors only. Performance of the models, expressed by predicted R-squared, was between 0.10 and 0.27, depending on the particular task condition. The time-on-task EEG spectral changes were characterized by broad changes in the alpha and frontal changes in the beta and gamma bands. We were able to identify a set of EEG spectral features that predict time-on-task. Our output is considered to be a measure of vigilance, reflecting the allocation of mental resources for the maintenance of attention.

Impact of methodological variability on EEG responses evoked by transcranial magnetic stimulation: A meta-analysis.

OBJECTIVE: This meta-analysis aimed to synthesize the existing literature on how different parameters of transcranial magnetic stimulation (TMS) and electroencephalogram (EEG) modulate the amplitudes of TMS-evoked potentials (TEPs). METHODS: A comprehensive search was run in PubMed and completed by Google Scholar to find articles studying healthy participants who underwent single pulse TMS-EEG sessions over their left primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). The amplitudes of the most commonly investigated TEP peaks for DLPFC stimulation (positives: 25, 60, 185 ms, negatives: 40, 100 ms) and M1 stimulation (positives: 30, 55,180 ms and negatives: 15, 45, 100, 280 ms) were extracted from studies. RESULTS: Cohen's d effect sizes were obtained in five independent categories that were stratified based on the stimulation, recording, and analyzing parameters. The overall effect sizes and equivalent means and standard deviations were computed within every category. CONCLUSIONS: This meta-analysis spotlights the need to rigorously and systematically control for the critical parameters in recording and analyzing TMS-EEG data to make the outcomes of further studies more comparable to the current body of literature. SIGNIFICANCE: The study demonstrates the possibility of reliably measuring TEPs by offering approximate ranges for every TEP peak in the most commonly targeted areas of DLPFC and M1.

Maternal Perceptions of Safeguards for Research Involving Children.

The vitality of clinical research and the health of the public relies on continued efforts to engage children in clinical research in a fully protected and ethically robust manner. Parents serve as proxy decision-makers assessing the risks and benefits of any given study in order to do what is in the best interest of their child. This study investigated maternal perceptions of research safeguards and mothers' willingness to enroll their children in clinical research studies. We hypothesized that mothers' perceptions of the protectiveness of safeguard procedures utilized in clinical research would be associated with mothers' willingness to enroll their children in research studies with such safeguards. Through a survey conducted via Amazon Mechanical Turk, mothers were asked to rate the perceived protectiveness of four safeguard procedures (confidential data coding, data and safety monitoring boards (DSMBs), institutional review boards (IRBs), and informed consent) and the degree to which they were willing to have their child participate in research studies in the presence of each of the four safeguard procedures. Respondents generally perceived safeguard procedures to be protective. Mothers' trust in researchers' honesty positively impacted perceptions of the protectiveness of research safeguard procedures and willingness to enroll children in research. Mothers of only healthy children perceived research safeguards to be more protective than mothers with at least one child with at least one health issue. This study provides insight into whether maternal perceptions of the protectiveness of different safeguard procedures are associated with mothers' willingness to enroll their children in research.

Factors Influencing Perceived Helpfulness and Participation in Innovative Research: A Pilot Study of Individuals with and without Mood Symptoms.

Little is known about how individuals with and without mood disorders perceive the inherent risks and helpfulness of participating in innovative psychiatric research, or about the factors that influence their willingness to participate. We conducted an online survey with 80 individuals (self-reported mood disorder [n = 25], self-reported good health [n = 55]) recruited via MTurk. We assessed respondents' perceptions of risk and helpfulness in study vignettes associated with two innovative research projects (intravenous ketamine therapy and wearable devices), as well as their willingness to participate in these projects. Respondents with and without mood disorders perceived risk similarly across projects. Respondents with no mood disorders viewed both projects as more helpful to society than to research volunteers, while respondents with mood disorders viewed the projects as equally helpful to volunteers and society. Individuals with mood disorders perceived ketamine research, and the two projects on average, as more helpful to research volunteers than did individuals without mood disorders. Our findings add to a limited empirical literature on the perspectives of volunteers in innovative psychiatric research.

Self-reported influences on willingness to receive COVID-19 vaccines among physically ill, mentally ill, and healthy individuals.

OBJECTIVE: Individuals with mental and physical disorders have been disproportionately affected by adverse health outcomes due to the COVID-19 pandemic, and yet vaccine hesitancy persists despite clear evidence of health benefits. Therefore, our study explored factors influencing willingness to receive a COVID-19 vaccine. METHODS: Individuals with mental illness (n = 332), physical illness (n = 331), and no health issues (n = 328) were recruited via Amazon Mechanical Turk. Participants rated willingness to obtain a fully approved COVID-19 vaccine or a vaccine approved only for experimental/emergency use and influences in six domains upon their views. We examined differences by health status. RESULTS: Participants across groups were moderately willing to receive a COVID-19 vaccine. Perceived risk was negatively associated with willingness. Participants differentiated between vaccine risk by approval stage and were less willing to receive an experimental vaccine. Individuals with mental illness rated risk of both vaccines similarly to healthy individuals. Individuals with physical illness expressed less willingness to receive an experimental vaccine. Domain influences differently affected willingness by health status as well as by vaccine approval status. CONCLUSIONS: Our findings are reassuring regarding the ability of people with mental disorders to appreciate risk in medical decision-making and the ability of people of varied health backgrounds to distinguish between the benefits and risks of clinical care and research, refuting the prevailing notions of psychiatric exceptionalism and therapeutic misconception. Our findings shine a light on potential paths forward to support vaccine acceptance.

Recent advances in atezolizumab-based programmed death-ligand 1 (PD-L1) blockade therapy for breast cancer.

Breast cancer, the most common cancer in women worldwide, is curable in âˆ¼ 70-80 % of patients with early-stage, non-metastatic disorder. However, advanced breast cancer with distant organ metastases is incurable with available therapeutics. Thus, scientists have sought emerging strategies for treating metastatic breast cancers., Immune checkpoint inhibitors (ICIs) have represented a significant development in breast cancer immunotherapy. Now, targeting immune checkpoint molecules (e.g., programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1)) have attracted increasing attention in the context of breast cancer therapy, chiefly triple-negative breast cancer (TNBC). Atezolizumab, a humanized IgG1 monoclonal antibody (mAb), has been designed to interfere with the binding of the PD-L1 ligand to its receptor. Targeting PD-L1 using atezolizumab potentiates T-cell responses to the tumor and consequently boosts tumor responses. The results of the IMpassion130 trial have recently led to the approval of the combination of atezolizumab and nab-paclitaxel to treat unresectable locally advanced or metastatic patients with PD-L1-positive TNBC. Herein, we summarize the clinical efficacy of atezolizumab in treating breast cancer and briefly discuss the possible immune-related adverse events (irAEs).

Stakeholders' Perspectives regarding Participation in Neuromodulation-Based Dementia Intervention Research.

This study evaluated stakeholders' perspectives regarding participation in two hypothetical neuromodulation trials focused on individuals with Alzheimer's disease and related disorders (ADRDs). Stakeholders (i.e., individuals at risk for ADRDs [n = 56], individuals with experience as a caregiver for someone with a cognitive disorder [n = 60], and comparison respondents [n = 124]) were recruited via MTurk. Primary outcomes were willingness to enroll (or enroll one's loved one), feeling lucky to have the opportunity to enroll, and feeling obligated to enroll in two protocols (transcranial magnetic stimulation, TMS; deep brain stimulation, DBS). Relative to the Comparison group, the At Risk group endorsed higher levels of "feeling lucky" regarding both research protocols, and higher willingness to participate in the TMS protocol. These findings provide tentative reassurance regarding the nature of decision making regarding neurotechnology-based research on ADRDs. Further work is needed to evaluate the full range of potential influences on research participation.

Comparison of lidocaine, lidocaine/epinephrine or bupivacaine for thoracolumbar paravertebral anaesthesia in fat-tailed sheep.

OBJECTIVE: To evaluate the speed of onset and duration of loss of sensation in the flank following paravertebral administration of lidocaine (with or without epinephrine) or bupivacaine. STUDY DESIGN: Blinded, randomized experimental study. ANIMALS: Nine healthy fat-tailed male lambs (mean weight ± SD, 22.9 ± 3 kg). Each animal was used twice. METHODS: Animals were allocated randomly to receive two of three treatments: lidocaine 2% (LID, n = 6), lidocaine with epinephrine 5 µg mL(-1) (LIDEP, n = 6) or bupivacaine 0.5% (BUP, n = 6). The sheep received a total volume of 9 mL (3 mL for each paravertebral nerve) of anaesthetic. Onset and duration of loss of sensation on the flank were evaluated using nociceptive stimuli (superficial and deep pin-prick and clamping with a haemostat). Values for heart (HR) and respiratory (f(R) ) rates, rectal and skin temperatures were recorded before and at predetermined intervals after paravertebral injection. Parameters were compared using anova followed by Duncan's test where relevant. RESULTS: Mean ± SD times to onset of loss of flank sensation following paravertebral administration of LID, LIDEP or BUP were 1.8 ± 1.2, 2.0 ± 0.9 and 3.6 ± 1.3 minutes, respectively. Durations of action in minutes were 65 ± 18, 95 ± 46 and 303 ± 98, respectively. Onset and duration of effects after BUP treatment were significantly longer than after LID or LIDEP (p < 0.05), but did not differ significantly between LID and LIDEP. No clinical signs of local anaesthetic toxicity were noticed and HR and f(R) remained stable with all protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Paravertebral administration of bupivacaine produces a longer duration of anaesthesia when compared to lidocaine with or without epinephrine and is indicated when prolonged flank surgery is to be performed.

1-(4-Meth-oxy-phen-yl)-4-(4-methyl-phen-yl)-3-phen-oxy-azetidin-2-one.

The central ß-lactam ring of the title compound, C(23)H(21)NO(3), is almost planar (r.m.s. deviation = 0.032Å). The meth-oxy-benzene ring is almost coplanar with the ß-lactam ring [dihedral angle = 1.87 (11)°], whereas the tolyl ring is almost normal to it [75.73 (12)°]. The dihedral angle between the ß-lactam ring and the O-bonded phenyl ring is 51.95 (12)°. An intra-molecular C-H⋯O inter-action generates an S(6) ring. The crystal structure features inter-molecular C-H⋯O hydrogen bonds, forming layers parallel to (011), and weak C-H⋯π inter-actions. Two aromatic π-π stacking inter-actions [centroid-centroid distances = 3.6744 (12) and 3.6799 (11) Å] are also observed.

6 Hz transcranial alternating current stimulation of mPFC improves sustained attention and modulates alpha phase synchronization and power in dorsal attention network.

Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation tool appropriate to modulate cortical oscillations and activity via the application of weak currents. The major goal of this study was to investigate the effects of medial Prefrontal Cortex (mPFC) stimulation on sustained attention task performance measured by Rapid Visual Information Processing (RVIP) task and the brain networks assumed to be critical to sustained attention. mPFC has been shown to be involved in sustained attention performance and as a main hub in default mode network (DMN). mPFC activity modulation via theta tACS was implemented in this study. This was a single blind study with 21 participants receiving active and sham stimulation with the electrodes on FPz and the Inion. tACS was able to impact different RVIP measures (total hits, A' (sensitivity to target), total correct rejection, etc.). Relative power spectrum density (PSD) analysis yielded significant increases in theta frequency mostly in the fronto-central regions after active tACS and current source density (CSD) analysis yielded significant power modulations in theta frequency band in post-central gyrus. Furthermore, phase locking value (PLV) analysis showed that there were significant changes in cortical connections in the Dorsal Attention Network (DAN) in alpha frequency band. This study showed that theta frequency tACS over mPFC, was able to produce significant modulations in an RVIP task and its associated brain networks in healthy participants.

The optimal cut-off point of vitamin D for pregnancy outcomes using a generalized additive model.

BACKGROUND & AIM: Several studies consider vitamin D deficiency as a modifiable risk factor for adverse pregnancy outcomes. However, there is no specific cut-off point for the serum level of this prohormone to identify high-risk pregnant women. This study aimed to determine the thresholds for the circulating levels of 25-hydroxyvitamin D (25(OH)D), associated with adverse pregnancy outcomes, including preterm labor, preeclampsia (PE), and gestational diabetes mellitus (GDM), using a generalized additive model. METHODS: This is a descriptive and analytical cross-sectional study carried out on the data collected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy. Of 1800 pregnant women, referred to the health centers of Masjed-Soleyman and Shushtar (Khuzestan Province, Iran), we used the data of 1763 pregnant women, whose serum vitamin D status during the third trimester of pregnancy was available. The datasets were randomly divided into training (70%) and validation (30%) subsets. The cut-off levels of 25(OH)D were identified for the low, moderate, and high risk of adverse pregnancy outcomes, according to generalized additive models (GAM) with smooth functions in the training data set. Then Generalized Linear Model (GLM), with logit link function was applied in the validation dataset to explore the relationships between the optimal vitamin D classification and adverse pregnancy outcomes after adjusting for the potential confounders. RESULTS: The optimal cut-off levels of 25(OH)D for the high, moderate, and low risk of GDM were ≤16, 16-26, and >26 ng/mL, respectively. Also, the optimal cut-off points of 25(OH)D for the high, moderate, and low risk of preterm delivery were ≤15, 15-21, and >21 ng/mL, respectively. Finally, the corresponding values for the high, moderate, and low risk of PE were ≤15, 15-23, and >23 ng/mL, respectively. The models were well-calibrated, based on the Hosmer-Lemeshow test. Results of the adjusted generalized linear model showed a significant increasing trend in the risk of pregnancy outcomes by decreasing 25(OH)D levels. CONCLUSION: In the preconception period, a 25(OH)D cut-off level of >15 ng/mL is recommended for the prevention of adverse pregnancy outcomes.